Insulin tightly regulates glucose uptake and metabolism, and therefore modulation of insulin activity and in turn glucose levels in the blood can have significant physiological effects. Many pathologies are either caused or enhanced by variations in insulin levels and the onset of insulin tolerance or resistance (i.e. a state where cells become less responsive or unresponsive to the insulin signal).
In type I diabetes (diabetes mellitus), the pancreatic production of insulin is greatly reduced. Hence type I diabetics need regular injections or perfusions of insulin to control their blood glucose to avoid deleterious consequences. Some type I diabetics also develop the “dawn syndrome”, a state of increased insulin resistance in the early hours of the morning.
In type II diabetes (non-insulin dependent diabetes or NIDD), individuals, usually overweight, develop an insulin resistance and hyperinsulinemia (high levels of insulin). Although some drugs may restore insulin sensitivity to a certain extent, type II diabetics usually have to change their lifestyle and lose weight to maintain control of their blood glucose level.
Individuals that have higher levels of growth hormone (GH), namely people affected with acromegaly or certain pituitary tumors, tend to develop insulin resistance. High blood levels of free fatty acids (FFA) and GH itself are thought to play an important role in the onset and maintenance of insulin resistance in these individuals.
Individuals that having lower than normal levels of GH, i.e. a GH deficiency, also tend to develop insulin resistance. GH deficiency favours fat mass gain and, therefore, insulin resistance. In addition, GH replacement therapy may exacerbate insulin resistance in these subjects through the production of free fatty acids.
Obesity also causes insulin resistance and, ultimately, NIDD. It has been shown that obese individuals have a lower than normal levels of GH. These results strongly suggest that the regulation and control of insulin, GH and body weight are all interrelated.
Insulin resistance may also increase under postprandial conditions (i.e. following feeding).
It would thus be desirable to have new strategies of therapeutic intervention relating to such processes.